CD4+ T cell-mediated granulomatous pathology in schistosomiasis is downregulated by a B cell-dependent mechanism requiring Fc receptor signaling.
The effector functions of CD4+ T lymphocytes are generally thought to be controlled by distinct populations of regulatory T cells and their soluble products. The role of B cells in the regulation of CD4-dependent host responses is less well understood. Hepatic egg granuloma formation and fibrosis in murine schistosomiasis are dependent on CD4+ lymphocytes, and previous studies have implicated CD8+ T cells or cross-regulatory cytokines produced by T helper (Th) lymphocytes as controlling elements of this pathologic process. In this report, we demonstrate that B cell-deficient (muMT) mice exposed to Schistosoma mansoni develop augmented tissue pathology and, more importantly, fail to undergo the spontaneous downmodulation in disease normally observed during late stages of infection. Unexpectedly, B cell deficiency did not significantly alter T cell proliferative response or cause a shift in the Th1/Th2 balance. Since schistosome-infected Fc receptor-deficient (FcR gamma chain knockout) mice display the same exacerbated egg pathology as that observed in infected muMT mice, the B cell- dependent regulatory mechanism revealed by these experiments appears to require receptor-mediated cell triggering. Together, the data demonstrate that humoral immune response/FcR interactions can play a major role in negatively controlling inflammatory disease induced by CD4+ T cells.
Jankovic
D
D
Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. djankovic@atlas.niaid.nih.gov
Cheever
A W
AW
Kullberg
M C
MC
Wynn
T A
TA
Yap
G
G
Caspar
P
P
Lewis
F A
FA
Clynes
R
R
Ravetch
J V
JV
Sher
A
A
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015536:Down-Regulation; D006099:Granuloma / Q000276:immunology / Q000469:parasitology / Q000473:pathology*; D008099:Liver / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D008107:Liver Diseases / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010063:Ovum / Q000276:immunology; D011961:Receptors, Fc / Q000502:physiology*; D012552:Schistosomiasis / Q000276:immunology / Q000473:pathology*; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D011961:Receptors, Fc